Partial Overview of Immune Response to SF-1019
Upon administration, SF-1019 initiates a rapid change in the proteome which persists for at least 24 hours. Mediators of the immune system (e.g., cytokines) are released in pulses during this period. The significance of some of these mediators and targeted entities are described in part below.
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Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a protein secreted by macrophages, T cells, mast cells, endothelial cells and fibroblasts.
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Interleukin-6 (IL-6) is a cytokine which can be secreted by T cells and macrophages to stimulate immune response to trauma, especially burns or other tissue damage. In terms of host response to a foreign pathogen, IL-6 has been shown to be required for resistance against the bacterium.
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Interleukin 12 (IL-12) is an interleukin that is naturally produced by macrophages and human B-lymphoblastoid cells (NC-37) in response to antigenic stimulation. IL-12 is involved in the differentiation of naïve T cells into Th1 Cells, which is important in resistance against pathogens. It is known as a T cell stimulating factor, which can stimulate the growth and function of T cells. It stimulates the production of interferon-gamma (IFN-?) and tumor necrosis factor-alpha (TNF-a) from T and natural killer (NK) cells, and reduces IL-4 mediated suppression of IFN-?. T cells which produce IL-12 have a coreceptor, CD30, which is associated with IL-12 activity. IL-12 plays an important role in the activities of NK cells and T lymphocytes. IL-12 mediates enhancement of the cytotoxic activity of NK cells and CD8+ cytotoxic T lymphocytes. There also seems to be a link between IL-2 and the signal transduction of IL-12 in NK cells. IL-2 stimulates the expression of two IL-12 receptors, IL-12R-ß1 and IL-12R-ß2, maintaining the expression of a critical protein involved in IL-12 signaling in NK cells. Enhanced functional response is demonstrated by IFN-? production and killing target cells.
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TNF-a Tumor necrosis factor (TNF, cachexin or cachectin and formally known as tumor necrosis factor-alpha) is a cytokine involved in systemic inflammation and is a member of a group of cytokines that all stimulate the acute phase reaction.
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Interferon-gamma (IFN-?) is a dimerized soluble cytokine that is the only member of the type II class of interferons. This interferon was originally called macrophage-activating factor.
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T cells belong to a group of white blood cells known as lymphocytes and play a central role in cell-mediated immunity. They can be distinguished from other lymphocyte types, such as B cells and NK cells by the presence of a special receptor on their cell surface that is called the T cell receptor (TCR). The abbreviation "T", in T cell, stands for thymus since it is the principal organ for their development.
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Natural killer (NK) cells are a form of cytotoxic lymphocyte which constitutes a major component of the innate immune system. NK cells play a major role in the host-rejection of both tumors and virally infected cells. They were named "natural killer" because of the initial notion that they do not require activation in order to kill cells which are "missing self" recognition ("missing-self" recognition is a term used to describe cells with low levels of MHC (major histocompatibility complex) class I cell surface marker molecules — a situation which could arise due to viral infection, or in tumors under strong selection pressure of T cells.
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